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OSD_GI > Colorectal Cancer > Flashcards

Colorectal Cancer Flashcards

(56 cards)

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1
Q

Of the following, which are tumor suppressor genes, which are oncogenes, & which are DNA repair enzymes?

p53, APC, hMSH2, SMAD, ras, MYH, DCC, c-myc, hMLH1

A

Oncogenes: ras, c-myc

Tumor Suppressor: APC, p53, DCC, SMAD

DNA Repair Genes: hMSH2, hMLH1, MYH

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2
Q

In what test is the K-Ras mutation detectable?

A

Mutations detectable in stool

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3
Q

Which gene, when inactivated, promotes the formation of other pro-oncotic mutations?

A

p53 (chromosome 17)
b/c it normally arrests the cell at the G1/S checkpoint, permitting the cell to locate & fix other mutations.
w/out this “repair time”, other mutations accumulate
(thus correlates w/ poor prognosis)

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4
Q

Name the gene defects in each step of the microsatellite instability pathway:

Normal
(a)  
-- DNA hypomethylation --
Early adenoma
(b)
Advanced Adenoma
(c)
Invasive cancer (& may lead to metastases)
A

a) APC
b) K-ras
c) p53

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5
Q

What is the rate-limiting step for initiation of most CRC?

A

APC mutation

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6
Q

~70% of FAP has what mutation?

A

APC mutation – 90% of these are a truncated APC protein

other 30% sporadic

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7
Q

What is the central mutational cause of Hereditary Non-Polyposis Colorectal Carcinoma?

A

Faulty DNA Mismatch Repair

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8
Q

Compare HNPCC & Sporadic Colorectal Carcinoma:

Age at diagnosis?

A

HNPCC: 45

Sporadic: 67

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9
Q

Compare HNPCC & Sporadic Colorectal Carcinoma:

Frequency of multiple colon cancers?

A

HNPCC: 35%

Sporadic: 4-11%

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10
Q

Compare HNPCC & Sporadic Colorectal Carcinoma:

Proximal locatin?

A

HNPCC: 72%

Sporadic: 35%

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11
Q

Compare HNPCC & Sporadic Colorectal Carcinoma:

Excess malignant tumors at other sites? (yes or no)

A

HNPCC: Yes

Sporadic: No

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12
Q

Compare HNPCC & Sporadic Colorectal Carcinoma:

Prognosis?

A

HNPCC: Favorable

Sporadic: Variable

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13
Q

What is the Amsterdam Criteria used for?

A

Used to determine if people have are likely to have Lynch Syndrome (HNPCC)

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14
Q

What are the Amsterdam Criteria?

A

3 : 2 : 1

3 relatives w/ an HNPCC-ass’d cancer (CRC, endometrial, SB, ureter/renal pelvis)

2 generations spanned

1 at age <50

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15
Q

Are DNA Replication Errors a common theme of:

  • HNPCC?
  • Sporadic Colorectal Carcinoma?
A

HNPCC: Yes (79%) (mostly Microsatellite Instability genes)

Sporadic: No (17%)

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16
Q

What is a polyp?

A

Visible protruding mass covered w/ mucosa

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17
Q

What does it mean to refer to polyps as sessile or pedunculated?

A

Sessile = Flat

Pedunculated = Stalked

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18
Q

What clinical diagnosis is made that calls for a prophylactic colectomy in young adulthood?

A

Familial Adenomatous Polyposis (FAP)

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19
Q

What type of gene is BAT26?

A

Microsatellite Instability gene

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20
Q

Some symptoms of Colorectal Carcinoma?

A
  • Melena/Hematochezia
  • Iron Deficiency Anemia
  • Change in bowel habits (stool caliber & frequency)
  • Abdominal pain
  • NO symptoms!
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21
Q

What is Carcinoembryonic Antigen?

A

Cell Surface Adhesion Glycoprotein that can be elevated in a variety of cancers such as Colorectal, Breast, Lung, & Gastric
- Expressed in 80-85% of Colon Cancers

  • It’s also elevated in non-cancer states such as Colitis, Pancreatitis, Cirrhosis, & Smoking
    (therefore not useful for screening)
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22
Q

Is Carcinoembryonic Antigen useful for screening?

A

No, but it may be useful for prognosis & follow-up

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23
Q

What are some poor prognostic factors for Colon Cancer?

Study These Flashcards
A
  • Obstruction or Perforation
  • Elevated Carcinoembryonic Antigen pre-op
  • Fewer nodes removed at surgery (minimum = 12)
24
Q

What are some “good” prognostic factors for Colon Cancer?

Study These Flashcards
A
  • Microsatellite Instability
  • – ass’d w/ HNPCC
  • Lower stage
25
3 major differences between Colon vs. Rectal cancers?
``` Colon = Melena Rectal = Hematochezia ``` Rectal = much HIGHER risk of relapse after surgery Rectal = usually require local RADIATION b/c of higher risk of relapse post-surgery
26
General Tx for Stages I-IV: Colon Cancer
``` Stage I (small tumor, negative nodes) - Surgical resection ``` ``` Stage II (bigger tumor, negative nodes) - Surgical resection ~~ Post-op Chemo if Stage IIb or perforation / obstruction / lymphovascular invasion ``` Stage III (positive nodes) - Surgical resection - Post-op Chemo Stage IV (distant metastases) - Chemotherapy - Surgery may play role if... - -- Bowel obstruction - -- Bleeding - -- Isolated liver metastases **note: rectal cancer is same, except add Radiation @ stages 2-3 & definite chemo @ 2
27
General Tx for Stages I-IV: Rectal Cancer
``` Stage I (small tumor, neg nodes) - Surgical resection ``` Stage II (bigger tumor, neg nodes) - Pre- or post-operative Radiation & Chemo - Surgical Resection - Postoperative Chemo Stage III (positive nodes) - Pre- or post-operative Radiation & Chemo - Surgical Resection - Post-operative Chemo Stage IV (distant metastases) - Chemotherapy - Most will need surgery or radiation for palliation of primary tumor
28
Fluorouracil- absorption?
Poor oral absorption (rapidly taken up into cells & phosphorylated) Capecitabine is oral prodrug
29
Fluorouracil- MOA?
Interferes w/ DNA - Inhibits Thymidylate Synthase - Incorporated into DNA Interferes w/ RNA
30
Fluorouracil- Toxicities?
- Myelosuppression - Mucositis - Diarrhea - Photosensitivity - Hand-foot Syndrome Uncommon: - Cardiac Syndrome - Biliary Fibrosis
31
A congenital deficiency of Dihydropyrimidine Dehydrogenase in 0.5% of population, puts you at risk for what?
Increased Fluorouracil toxicity
32
Leucovorin- use/effects?
Augments the cytotoxicity/effectiveness of Fluorouracil Leucovorin is Reduced Folate
33
What is Capecitabine?
Oral prodrug of Fluorouracil | b/c Fluorouracil is poorly absorbed
34
What are the 2 current standard drugs used for adjuvant therapy of Colorectal Cancer?
Fluorouracil - - Capecitabine (oral prodrug) - - Leucovorin (augments effect) Oxaliplatin
35
Fluorouracil is a _____ _____ (type of drug)
Halogenated Pyrimidine
36
Oxaliplatin- MOA?
Mainly forms N7-d(GpG) intrastrand adduct - blocks DNA replication - blocks Transcription *adduct = combo of 2 or more compounds
37
How is resistance to Oxaliplatin mediated?
Nucleotide Excision Repair Genes
38
Oxaliplatin- method of delivery?
IV only (undergoes non-enzymatic conversion)
39
Oxaliplatin- Toxicities?
- Myelosuppression - Peripheral neuropathy - Diarrhea - Mucositis
40
Metastatic (stage IV) Colorectal Cancer: - Median Survival? - Cure?
~2 yrs. Currently no cure
41
Colorectal Cancer: Hematogenous & Local metastatic tendencies?
Hematogenous: - Liver - Lungs - Bone, Brain Local - Intra-abdominal - Intra-pelvic
42
Drugs for Metastatic (stage IV) Colorectal Cancer?
- Fluorouracil - Oxaliplatin - Irinotecan - Bevacizumab - Cetuximab/Panitumomab
43
Irinotecan- MOA?
Topoisomerase I inhibitor
44
Irinotecan- Resistance mechanisms?
- Impaired transport/Enhance efflux - Topoisomerase mutations - Enhanced metabolism
45
Irinotecan- method of delivery?
IV only
46
Irinotecan- Toxicities?
- Myelosuppression - Diarrhea - Mucositis
47
Bevacizumab- MOA?
Humanized anti-VEGF antibody
48
Bevacizumab- method of delivery?
Given by vein w/ chemotherapy
49
Bevacizumab- Toxicities?
- Hypertension - Thrombosis - Bleeding - Infusion rxns - Inc toxicity of chemotherapy
50
Cetuximab/Panitumomab- MOA?
- Antibodies directed at extracellular domain of EGFR | - Block binding of EGF to receptor
51
Cetuximab/Panitumomab- Toxicities?
- Rash - Diarrhea - Mucositis
52
Cetuximab/Panitumomab- Mechs of Resistance?
Activating mutations in K-ras & BRAF render cells resistant to antibodies (these convey poor natural history)
53
@ what stage does post-operative Chemotherapy become standard use in Colorectal Cancer?
Stage III | sometimes used in Stage II
54
@ what stage does Chemotherapy become standard use in Rectal Cancer?
Stages II & III
55
@ what stage does Radiation become standard use in Rectal Cancer?
Stages II & III
56
T or F? Stage IV Colorectal Cancer is incurable, but Tx prolongs life.
True

OSD_GI (13 decks)

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